Cytomegalovirus or CMV, is the virus behind the developing of permanent problems such as deafness, blindness and intellectual disability retardation in more than 5,000 newborns in the US each year. It affects more live births than both Down Syndrome and Fetal Alcohol Syndrome, and direct economic costs of CMV infection exceed $2 billion annually.
Despite this, there is currently no available vaccine and a large proportion of the developed world have never even heard of the disease.
In June this year, a company called VBI Vaccines, Inc. - Ordinary Shares (NASDAQ:VBIV) kicked off a phase I clinical trial investigating the safety and efficacy of VBI101, a development stage CMV vaccine targeting the unmet need. It is still in its early days, the development process for a vaccine like this could be anywhere between five and ten years, not accounting for setbacks, but if the company can get the drug approved, it would be a major step forward for global healthcare.
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Here is a look at the trial in question ahead of any data releases, and what we are looking for as indicative of efficacy when top line hits press.
First, let's take a look at the drug itself. VBI101 is a vaccine borne out of VBI's proprietary vaccine creating technology, the eLVP platform. Back in 2009, a scientist named Dr. Robert Pass conducted a phase II clinical trail (note: this was independent and nothing to do with VBI) investigating the efficacy of a CMV vaccine based on what's called the gB antigen. Our immune systems form immunity based on the recognition of antigens, which are what viruses secrete in our bodies. Vaccines are artificial introductions of these antigens. The gB antigen is the antigen expressed by the CMV virus. In the Pass phase II, the data demonstrated that the immune system responded to the gB antigen based vaccine with a success rate of 50%; i.e. the vaccine created an immunity to the CMV virus in 50% of patients that took it. This isn’t a great rate, but it served as proof of concept for VBI, and the company set about developing a gB based CMV vaccine with an improved immunogenicity than the Pass vaccine. VBI101 is the outcome.
The vaccine has three key improvements designed to help improve its efficacy. The first, it is built on the company's proprietary eVLP platform, which is designed to mimic the natural virus as closely as possible (size, shape etc.), which increases the immunogenicity. The second, VBI101 has an altered form of the gB antigen called gB-G, which provokes an even stronger response from the immune system than does unmodified gB. The third, it has aluminum phosphate (alum) mixed in with it. Alum is used in a huge number of vaccines already as an adjuvant, it can help lengthen the time for which a vaccine remains effective.
In preclinical studies, VBI has shown that each of these improvements individually induce a five-fold improvement in immunogenicity over the original Pass gB vaccine and that the immunogenicity rate compares to that of patients who are naturally immune to CMV (somewhere around the 90% level).
The key thing now is to reproduce these preclinical findings in human trials.
So, as mentioned, the trial started in June, and it is a circa twenty-month trial with a target primary completion date of August 2017, and full completion date of December 2017. As far as clinical trials go, that is on the short side, which bodes well for future trial protocol. The population size is targeted at 125, but there is also a large number of control individuals (the above mentioned naturally immune individuals that will widen the final data pool) but are not included as patients in the trial.
The 125 patients were split in to five separate, blinded, groups at the beginning of the trial. Three of these groups will take varying doses (0.5 μg, 1.0 μg and 2.0 μg) of VBI101A, which is the alum-combined vaccine. One group will take 1.0 μg of VBI101, but without the alum adjuvant. The final group will take a placebo. All doses across the five groups will be intramuscular injection administration, and take place on day 0, day 56 and day 168.
The primary endpoint of the trial is occurrence of adverse events (AEs) from first injection to day 336 or early withdrawal (EW), six months' post dose three in all participants, in all groups. It is a safety trial first and foremost. The secondary endpoints, however, are the more interesting of the study. There are a few target points, but the most important are antibody binding titers and avidity measurement directed against the gB component of the vaccine and neutralizing antibody titers against CMV infection of fibroblast and epithelial cells. If we see any activity against either of these endpoints, it would suggest the efficacy reported in the preclinical models is replicable at the human level. In turn, it would be a big boost for VBI and the CMV space.
From a timeframe perspective, we probably won't see any interim (although it is only observer blind, so there is a chance that we might), and we are targeting the primary completion as an initial insight date. Beyond that, we should see topline hit press at the end of the fourth quarter of 2017.
VBI is developing a couple of other candidates. It has got a hepatitis B vaccine that already markets in fifteen countries, but is targeting the US and Europe near term. It has also got a brain cancer vaccine based on the same technology as the CMV vaccine. This one, however, is probably its largest near term potential. Analysts expect demand for a CMV vaccine to exceed 7.6 million doses by 2030. If the company prices its VBI101 at the same price as the current SOC HPV vaccine, $140, it could be looking at a market worth more than $1 billion a year, just for its CMV candidate.
As noted, VBI101 is a long way from commercialization, but it is one of the most exciting stories in healthcare today, and we are keeping a close eye on its progress going forward.
Disclosure: I do not own shares in any of the company's discussed in this article and have no intentions of initiating a position at any point across the next 72 hours.
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